*3.8. Susceptibility of K133WT and K133AS-R Parasites in the Presence of the AQP1 Inhibitor and Modulator of ABC Transporters*

The susceptibility of K133WT and K133AS-R parasites towards artesunate was determined in the presence of AQP1 inhibitor and modulator of ABC transporters, verapamil. The cytotoxicity of the AQP1 inhibitor or verapamil determined for host macrophages (mice PECs) by the MTT assay revealed that the cytotoxic concentration 50% (CC50) of the AQP1 inhibitor was 233.47 ± 40.19 and that of verapamil was 111 ± 14.17 (Figure S2). The IC<sup>50</sup> of K133AS-R parasites towards artesunate significantly decreased by 1.9-fold in the presence of the AQP1 inhibitor and 2.2-fold in the presence of verapamil at the promastigote stage (Figure 8A). Surprisingly, at the intracellular amastigote stage, K133WT parasites showed a significant increase of >4-fold in the IC50; however, no significant alteration was observed in the IC<sup>50</sup> of K133AS-R parasites towards artesunate in the presence of the AQP1 inhibitor. Further, in the presence of verapamil at the amastigote stage, IC50b of artesunate for the K133AS-R parasites decreased by 2-fold (Figure 8B). However, there was no significant alteration in IC<sup>50</sup> of K133WT parasites in the presence of the AQP1 inhibitor at the promastigote stage and in the presence of verapamil at the promastigote or amastigote stage (Figure 8A,B).
